W. Daniel Jackson

Efficacy, Dose Reduction, and Resistance to High-Dose Fluticasone in Patients With Eosinophilic Esophagitis

BACKGROUND & AIMS We evaluated the efficacy and safety of high-dose swallowed fluticasone propionate (FP) and dose reduction in patients with eosinophilic esophagitis (EoE) and analyzed esophageal transcriptomes to identify mechanisms. METHODS We conducted a randomized, multisite, double-blind, placebo-controlled trial of daily 1760 mcg FP in participants age 3-30 years with active EoE. Twenty-eight participants received FP, and 14 participants received placebo. After 3 months, participants given FP who were in complete remission (CR) received 880 mcg FP daily, and participants in the FP or placebo groups who were not in CR continued or started, respectively, 1760 mcg FP daily for 3 additional months. The primary end point was histologic evidence for CR. Secondary end points were partial remission (PR), symptoms, compliance, esophageal gene expression, esophageal eosinophil count, and the relationship between clinical features and FP responsiveness. RESULTS After 3 months, 65% of subjects given FP and no subjects given placebo were in CR (P = .0001); 12% of those given FP and 8% of those given placebo were in PR. In the FP group, 73% of subjects remained in CR, and 20% were in PR after the daily dose was reduced by 50%. Extending FP therapy in FP-resistant participants did not induce remission. FP decreased heartburn severity (P = .041). Compliance, age, sex, atopic status, or anthropomorphic features were not associated with response to FP. Gene expression patterns in esophageal tissues of FP responders were similar to those of patients without EoE; there was evidence for heterogeneous steroid signaling in subjects who did not respond to FP and preliminary evidence for transcripts predictive of FP responsiveness. CONCLUSIONS Daily administration of a high dose of FP induces histologic remission in 65%-77% of patients with EoE after 3 months. A 50% dose reduction remained effective in 73%-93% of patients who initially responded to FP. Nonresponders had evidence of steroid resistance; histologic and molecular markers may predict resistance. Clinicaltrials.gov number: NCT00426283.

Elimination of soybean lipid emulsion in parenteral nutrition and supplementation with enteral fish oil improve cholestasis in infants with short bowel syndrome.

BACKGROUND Parenteral nutrition-associated liver disease (PNALD) is a potentially fatal complication for children with intestinal failure. Fish oil-based lipid emulsions have shown promise for the treatment of PNALD but are not readily available. Six cases are presented in which cholestasis resolved after soybean lipid emulsion (SLE) was removed from parenteral nutrition (PN) and enteral fish oil was given. METHODS A retrospective review at a tertiary childrens hospital (July 2003 to August 2008) identified 6 infants with intestinal failure requiring PN for >6 months who developed severe hepatic dysfunction that was managed by eliminating SLE and providing enteral fish oil. RESULTS Twenty-three infants with short bowel syndrome requiring prolonged PN developed cholestasis. SLE was removed in 6 of these patients, and 4 of the 6 received enteral fish oil. Standard PN included 2-3 g/kg/d SLE with total PN calories ranging from 57 to 81 kcal/kg/d at the time of SLE removal. Hyperbilirubinemia resolved after elimination of SLE within 1.8-5.4 months. Total PN calories required to maintain growth generally did not change. CONCLUSIONS Temporary elimination of SLE and supplementation with enteral fish oil improved cholestasis in PN-dependent infants. Further trials are needed to evaluate this management strategy.

Improving the Prevention, Early Recognition, and Treatment of Pediatric Obesity by Primary Care Physicians

To determine if participation in a learning collaborative (LC) would improve care processes for prevention, early recognition, and treatment of childhood obesity by primary care physicians (PCP), the authors conducted pre-post evaluations of the use of obesity related care processes by 18 primary care practices following participation in a 9-month LC based on the Model for Improvement. Prior to the LC, chart audits revealed that 55% of patients had a BMI recorded; this rose to 97% of patients at its conclusion. Following the LC, 11 practices had implemented systematic prevention advice to parents of infants compared with 3 prior to the LC. All practices developed plans for evaluation and management of children with an elevated BMI. Participation in an LC increased the number of primary care practices that provided anticipatory guidance regarding obesity prevention and that identified and treated overweight or obese children.

Growth of children with a functionally single ventricle following palliation at moderately increased altitude

The bidirectional Glenn and Fontan procedures are empirically performed as interim and definitive procedures in children with a functionally single ventricle. The optimal stage of palliation, nonetheless, remains unknown. During childhood, growth is a fundamental measure of response to therapy. Growth may be influenced by the degree of cyanosis, the volume load on the ventricle, and cardiac performance. Thus, the weight and stature of children with a functionally single ventricle who underwent a bidirectional Glenn procedure or a Fontan procedure were studied to determine the effect of each intervention on growth. Z scores for weight and stature were retrospectively determined prior to palliation, at yearly intervals for 4 years, and from long-term measurements until 18 years of age in all patients with at least 2 years of observation following palliation. Growth was evaluated in 54 patients with a bidirectional Glenn procedure, and 65 patients with a Fontan procedure. The Z scores for weight were improved after each method of surgical palliation. Stature, however, was improved only following the bidirectional Glenn procedure. Growth was impaired in patients who developed protein losing enteropathy. Weight improved only during the initial 2 years after the Fontan procedure in patients who had a surgical fenestration. Over the long-term, patients who underwent a Fontan procedure were more likely to have a Z score less than -2.0 for weight and stature than patients who underwent only a bidirectional Glenn procedure. Late mortality and the incidence of heart transplantation were increased in patients who experienced a decrease in their rate of growth, defined as a negative change of more than one Z score in weight or stature, following the Fontan procedure. In conclusion, at moderately increased altitude, children with a functionally single ventricle grow more appropriately following the bidirectional Glenn procedure than following the Fontan procedure. A decrease in the rate of growth is associated with a poor prognosis following the Fontan procedure.

Gastrointestinal polyposis in childhood: clinicopathologic and genetic features.

Gastrointestinal polyps and certain extraintestinal lesions in children may herald a hereditary polyposis syndrome, with an increased risk of neoplasia and other health problems for both children and their relatives. The availability of molecular/genetic screening tests has increased early diagnosis of younger members of known polyposis families. This article reviews the gross and microscopic features of polyposis syndromes of childhood and summarizes the molecular/genetic advances in this field. Clinical management is also briefly discussed.

Correlation of Cholestasis With Serum Copper and Whole-Blood Manganese Levels in Pediatric Patients

Many institutions reduce or eliminate copper (Cu) and manganese (Mn) in parenteral nutrition (PN) solutions when cholestasis develops. Little data exist to support this practice. Fifty-four subjects with known serum Cu, whole-blood Mn, and serum-conjugated bilirubin levels were evaluated in this prospective, observational study. Subjects ranged in weight from 760 g to 65.2 kg. Subjects weighing <25 kg received a daily parenteral dose of 20 microg/kg Cu and 5 microg/kg Mn. Subjects weighing > or =25 kg received a dose of 500 microg/d Cu and 150 microg/d Mn. Cholestasis was defined as a conjugated bilirubin level > or =2 mg/dL. Of the 54 subjects, 20 had cholestasis. Fifteen patients had elevated Cu levels, and 21 had high Mn levels. Seven of the subjects had both high Cu and high Mn levels. The regression model comparing cholestasis as a predictor of high, low, or normal Cu level was not significant (P = .9588). Cholestasis was not a significant predictor of high, low, or normal Mn levels (P = .6533). No correlation between Cu and Mn levels was found. The authors found no significant relationship between conjugated serum bilirubin levels > or =2.0 mg/dL, serum Cu, and whole-blood Mn levels. They found insufficient evidence to support the practice of dosing Mn from a Cu level or vice versa. They recommend obtaining Cu and Mn levels on all pediatric patients who develop cholestasis prior to adjusting parenteral doses and at regular intervals for all long-term PN patients.

Clinical variables as prognostic tools in pediatric-onset ulcerative colitis: A retrospective cohort study

Background: Clinical variables may identify a subset of patients with pediatric‐onset ulcerative colitis (UC) (≤18 years at diagnosis) at risk for adverse outcomes. We postulated that routinely measured clinical variables measured at diagnosis would predict colectomy in patients with pediatric‐onset UC. Methods: We conducted a chart review of patients with pediatric‐onset UC at a single center over a 10‐year period. We compared patients with and without colectomy across several variables, used proportional hazards regression to adjust for potential confounders, and assessed the ability of a UC risk score to predict colectomy. Results: Among 470 patients with inflammatory bowel disease ICD9‐coded encounters, 155 patients had UC and 135 were eligible for analysis. The 1‐ and 3‐year colectomy rates were 16.7% (95% confidence interval [CI]: 11.0%–24.8%) and 35.6% (26.7%–45.4%). White blood cell (WBC) count and hematocrit measured at diagnosis were associated with colectomy at 3 years, even after correcting for potential confounding variables. A UC Risk Score derived from the WBC count and hematocrit was strongly associated with colectomy risk, with a high negative predictive value (NPV) for colectomy at 1 and 3 years (NPV = 0.95 and 0.89, respectively), but low positive predictive value (PPV = 0.22 and 0.38, respectively). Conclusions: A risk score calculated from WBC and hematocrit measured at diagnosis was associated with, but incompletely predictive of, colectomy in pediatric‐onset UC. These data suggest 1) routinely measured clinical variables may have a prognostic role in risk stratification, and 2) multicenter prospective studies are needed to optimize risk stratification in pediatric UC. Our findings have impact on the design of such studies. (Inflamm Bowel Dis 2011;)

Adverse outcomes associated with gastroesophageal reflux disease are rare following an apparent life‐threatening event

OBJECTIVE To evaluate for adverse outcomes associated with gastroesophageal reflux disease (GERD) following an apparent life-threatening event (ALTE) and potential risk factors of these outcomes. STUDY DESIGN Retrospective cohort study of well-appearing infants (<12 months) admitted for ALTE. Patients were followed for adverse outcomes associated with GERD (including aspiration pneumonia, failure-to-thrive, or anti-reflux surgery), second ALTE, or death. Risk factors evaluated included: age, prematurity, gender, previous event, diagnosis of GERD, gastrointestinal (GI) testing positive for gastroesophageal reflux, length of stay (LOS), and neurologic impairment diagnosed in follow-up. RESULTS Four hundred sixty-nine patients met inclusion criteria, mean age was 45 days, 110 (22%) were premature. Patients were followed for an average of 7.8 years; 3.8% of all patients had an adverse outcome associated with GERD. The only significant risk factors were a longer LOS, and development of neurological impairment. A diagnosis of GERD and positive reflux testing during the initial hospitalization were not associated with adverse outcomes associated with GERD. CONCLUSIONS Adverse outcomes associated with GERD are rare following an ALTE. Patients who developed neurological impairment and a longer initial LOS were at higher risk for developing these outcomes. Positive testing for gastroesophageal reflux during hospitalization for ALTE did not predict adverse outcomes associated with GERD.

Foreign body impaction as presentation of eosinophilic esophagitis.

Esophageal foreign body is a frequent pediatric presentation, and eosinophilic esophagitis (EoE) is an important underlying disease. To determine characteristics common in the presentation of esophageal foreign body indicative of underlying EoE and reach a recommendation for the appropriate scenario in which to obtain esophageal mucosal biopsy, 312 pediatric esophageal foreign bodies requiring operative removal were reviewed. Patients older than 18 years or with a known history of esophageal surgery or pathology were excluded. Eligibility criteria were met in 271 cases. Twenty-seven patients were biopsied, and 18 were diagnosed with EoE. The following factors were identified in the EoE population: food impaction (89%), older age (average 12.2 years), male sex (78%), atopic disease (61%), previous esophageal foreign body or frequent dysphagia (83%), and endoscopic abnormalities (100%). These factors are all associated with an underlying diagnosis of EoE, and patients meeting these criteria should be strongly considered for intraoperative esophageal mucosal biopsy.

A unique presentation: dorsal agenesis of the pancreas manifesting as pancreatic exocrine insufficiency in the absence of diabetes mellitus in an 8-year-old boy.

To the Editor: Complete or partial agenesis of the dorsal pancreas is a rare anomaly that may be asymptomatic, detected incidentally on imaging, or associated with clinical abnormalities. We describe a case of agenesis of the dorsal pancreas in an 8-year-old male manifesting as exocrine pancreatic insufficiency without diabetes mellitus. The absence of diabetes mellitus in this setting is, to the best of our knowledge, unique. An 8-year-old male was referred for evaluation for diarrhea of suspected pancreatic origin. He had been previously healthy and in the 90th percentile for both height and weight until the previous year when his growth curve peaked and he began to lose weight and complain of fatigue. He had lost approximately 20 pounds in a period of 8– 9 months. He was not diabetic, with a normal HgbA1C. He developed bulky, greasy stools suggestive of steatorrhea as confirmed by fecal fat studies, and was producing six large stools daily. His diarrhea resolved completely with oral, coated pancreatic enzyme supplementation and his weight began to increase again. His only other medical problem was asthma for which he took fluticasone, montelukast sodium, and albuterol. There was no history of acute pancreatitis. His physical exam was unremarkable, and he had no abdominal pain. Complete blood count, comprehensive metabolic panel, and liver function testing were normal. His amylase and lipase levels were normal. Autoimmune markers including anti-nuclear antibody and IgG4 levels were normal. Genetic testing for SPINK1 and PRSS1 was negative. CFTR mutation testing demonstrated heterozygous presence of the non-disease polymorphism M470V and 70/70 variant. A CT scan demonstrated a pancreatic head only, without visualization of the pancreatic body or tail. MRI with MRCP visualized the pancreatic head only. Radial EUS was performed at 7.5 MHz with Doppler ultrasound (Fig. 1). The pancreatic head and ventral duct system were normal in appearance. There was only a small amount of pancreatic parenchyma seen above the level of the pancreatic head. The pancreatic duct had a diameter of 1.7 mm. The parenchyma had a normal appearance. The pancreatic parenchyma above this level ended abruptly. In addition, the pancreatic duct did not extend to the end of the visualized parenchyma. No parenchyma or duct was seen to suggest a proper pancreatic body or tail. Agenesis of the dorsal pancreas is a rare and infrequently reported developmental anomaly. Complete and partial agenesis may occur [1–3]. Partial agenesis has been reported more frequently and is characterized by the finding of a minor papilla and remnant of the accessory duct and pancreatic body parenchyma, which are absent in complete dorsal agenesis. Complete agenesis of the dorsal pancreas has historically been associated with diabetes mellitus [4]. Prevalence of exocrine dysfunction is much less common, with only one case of dorsal agenesis of the pancreas in association with exocrine pancreatic insufficiency that could be identified in the literature, and this patient had concomitant diabetes mellitus [5]. Our case is B. W. Doxey D. G. Adler Division of Gastroenterology, Hepatology, and Nutrition, University of Utah Health Sciences Center, Salt Lake City UT, USA